Gerhard P. J. Schröter

Use of Cytomegalovirus Immune Globulin to Prevent Cytomegalovirus Disease in Renal-Transplant Recipients

We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.

Liver Transplantation with Use of Cyclosporin a and Prednisone

THE difficulties in consistently prolonging survival after orthotopic liver transplantation have been documented by us1 and by Calne.2 In this report we describe a new trial of orthotopic liver tra...

Fifteen Years of Clinical Liver Transplantation

Liver transplantation in humans was first attempted more than 15 yr ago. The 1-yr survival has slowly improved until it has now reached about 50%. In our experience, 46 patients have lived for at least 1 yr, with the longest survival being 9 yr. The high acute mortality in early trials was due in many cases to technical and management errors and to the use of damaged organs. With elimination of such factors, survival increased. Further improvements will depend upon better immunosuppression. Orthotopic liver transplantation (liver replacement) is the preferred operation in most cases, but placement of an extra liver (auxiliary transplantation) may have a role under special circumstances.

Liver transplantation for advanced liver disease with alpha-1-antitrypsin deficiency

ALPHA-1-antitrypsin deficiency associated with chronic obstructive airway disease was recognized in 1963 by Laurell and Ericksson.1 In 1969, Sharp2 described the first cases of alpha-1-antitrypsin-...

Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus.

Nine of 48 adult patients who underwent orthotopic liver transplantation developed significant clinical neurological abnormalities recognized shortly after operation. Decrease in consciousness occurred with resultant coma, focal and generalized seizures and the occasional appearance of a state of akinetic mutism. Neuropathological abnormalities consisted of multifocal areas of infarction in cerebral cortex and basal ganglia in five patients, central pontine myelinolysis in five (often more extensive than usually reported), Wernickes encephalopathy in three, glial nodules in two, and fungal abscesses in one. Alzheimer II astrocytosis was found in all brains available for retrospective study. There was direct evidence in two of the patients that air embolization from the homografts had occurred. Correlation of this with the brain infarcts in these and other cases seems reasonable. The ease with which air passed to the systemic circulation is explicable by the right to left venous-arterial shunts that are common in chronic liver disease. With the delineation of this cause for the neurologic complications, measures to prevent it in future cases have been described.

Cholangitis after the Kasai operation for biliary atresia

One hundred seventy-nine episodes of cholangitis in 28 consecutive patients having a Kasai operation for biliary atresia during the past 3 1/2 years were analyzed. The diagnosis was made primarily on the basis of unexplained fever (greater than 38.0 degrees C). An increase in serum bilirubin or a decrease in bile volume and in bile bilirubin concentration were often confirmatory, but other laboratory data including serum hepatic enzymes and blood and bile culture data were of little or inconsistent value. All patients were treated with systemic antibiotics. The best results were obtained with third-generation cephalosporins or imipenemcilastatin with the addition of aminoglycosides in recalcitrant cases. Antibiotic therapy was modified if defervescence did not occur within the first 24 hours. Cholangitis refractory to antibiotics was aggressively treated with pulse steroid therapy, and in some cases, operative intervention, both with good clinical success (60% and 73%, respectively).

Thoracic duct fistula and renal transplantation.

Thoracic duct drainage (TDD) was established for 21 – 115 days in 40 kidney recipients with an average removal per patient day of 4.7 I lymph and 1.88 billion cells. Cellular and humoral immunity were depressed. TDD and immunosuppressive drugs were started at transplantation in 35 recipients of cross-match negative grafts. Although the results were better than in precedent non-TDD controls, eight patients rejected their grafts before a full TDD effect, and three of the eight developed predominantly anti-B lymphocyte cytotoxic antibodies which were probably responsible for positive cross-matches with their next donors. With continuing TDD, all eight patients had good initial function after early retransplantation. In five more “nontransplantable” patients with performed cytotoxic antibodies, TDD was started 30–56 days before transplantation. In these five pretreated patients, antibodies persisted with positive antidonor cross-matches. Hyperacute rejection occurred repeatedly in two patients with high anti-T (and anti-B) titers, but was surmounted in three patients with lower titers. From the clinical and immunologic data, we have concluded that TDD should be used for pretreatment of all cases with or without prior antibodies, and have suggested an adjustable management plan that takes into account new developments in antibody monitoring.

Immunosuppression, liver injury, and hepatitis in renal, hepatic, and cardiac homograft recipients: with particular reference to the Australia antigen.

RENAL homograft recipients have been reported to have a high incidence of livu disease in the post-transplantation period.2f• 29. 31. 56. 65, 70 It was assumed that the immunosuppressive agents were responsible, either by their hepatotoxicity or because the consequent weakening of the host immune system permitted the frequent development of virus hepatitis. An accurate distinction between these two general possibilities was not feasible until recently. Then, with the description of tests which permitted identification of the hepatitis associated or Australia (Au) antigen, 7 , 9, 58 it became possible to deciSively study at least one variety of virus hepatitis in transplant recipients. In this communication, a series of observations related to the problem of hepatic damage with or without hepatitis in a large transplantation program will be presented. These observations will include: (1) The

CURRENT POLICIES IN HEPATIC TRANSPLANTATION: CANDIDACY OF PATIENTS WITH ALCOHOLIC LIVER DISEASE OR PREFORMED ANTIDONOR ANTIBODIES AND A REAPPRAISAL OF BILIARY DUCT RECONSTRUCTION*

Eighty-two patients have been treated by orthotopic hepatic transplantation in Denver since 1963. Eighteen and nine patients have lived for 1 year and 2 years posttransplantation, respectively. Thirteen recipients are still alive from 3 weeks to almost 5 years postoperatively. Current policy has been reexamined in 3 areas in light of this experience. First, only the occasional potential recipient with alcoholic liver disease, free of infectious or other complications, is an acceptable candidate for this procedure. Second, the presence in the recipients serum of preformed anti-red cell or lymphocytotoxic antibodies to his donor is a relative, but not an absolute, contraindication to hepatic transplantation, since the liver appears to be more resistant to hyperacute rejection than the kidney. Finally, a 6-point program has been outlined for establishing and evaluating bile drainage, in order to prevent or remedy both the technical and bacteriologic complications associated with faulty biliary reconstruction.

Autopsy findings in a long-surviving liver recipient

IT has been a little more than five years since the first extended survival was achieved after human liver transplantation, and for that reason individual cases are still of special interest. For a...